Abstract
Mutations in cereblon (CRBN), a substrate binding component of the E3 ubiquitin ligase complex, cause a form of mental retardation in humans. However, the cellular proteins that interact with CRBN remain largely unknown. Here, we report that CRBN directly interacts with the α1 subunit of AMP-activated protein kinase (AMPK α1) and inhibits the activation of AMPK activation. The ectopic expression of CRBN reduces phosphorylation of AMPK α1 and, thus, inhibits the enzyme in a nutrient-independent manner. Moreover, AMPK α1 can be potently activated by suppressing endogenous CRBN using CRBN-specific small hairpin RNAs. Thus, CRBN may act as a negative modulator of the AMPK signaling pathway in vivo.
Copyright © 2011 Elsevier B.V. All rights reserved.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
AMP-Activated Protein Kinases / genetics
-
AMP-Activated Protein Kinases / metabolism*
-
ATP-Dependent Proteases
-
Adaptor Proteins, Signal Transducing
-
Animals
-
Carrier Proteins / genetics
-
Carrier Proteins / metabolism*
-
Cell Line
-
DNA, Complementary / genetics
-
Enzyme Activation
-
Gene Expression Regulation
-
Humans
-
Mice
-
Nerve Tissue Proteins / genetics
-
Nerve Tissue Proteins / metabolism*
-
Peptide Hydrolases / genetics
-
Peptide Hydrolases / metabolism*
-
Protein Binding
-
Rats
-
Ubiquitin-Protein Ligase Complexes
-
Ubiquitin-Protein Ligases
Substances
-
Adaptor Proteins, Signal Transducing
-
CRBN protein, human
-
CRBN protein, rat
-
Carrier Proteins
-
Crbn protein, mouse
-
DNA, Complementary
-
Nerve Tissue Proteins
-
Ubiquitin-Protein Ligase Complexes
-
Ubiquitin-Protein Ligases
-
AMP-Activated Protein Kinases
-
Peptide Hydrolases
-
ATP-Dependent Proteases